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Sarcolemmal membranes from pig hearts express a homogenous class of binding sites for [3H]PGE1. Competition binding studies with EP receptor suptype selective ligands suggest an EP3 receptor subtype. The GTP analogue GTP gamma S reduced affinity without changing binding capacity, indicating a G protein coupled EP3 receptor. Regional myocardial ischemia (60 min) in anesthetized, open-chest pigs caused a 50% increase of the number of binding sites while GTP gamma S still decreased [3H]PGE1 binding, suggesting intact G protein coupling. Myocardial ischemia may, therefore, modify myocardial actions of prostaglandins.

P-selectin is an adhesion receptor for leukocytes that is expressed on activated platelets and endothelial cells. The surface expression of P-selectin is tightly regulated through signals in the cytoplasmic domain that mediate sorting into secretory granules, internalization into coated pits, and targeting to lysosomes for degradation. Like the other selectins, P-selectin binds sialylated, fucosylated carbohydrate ligands such as sialyl Lewis x. However, it binds with much higher affinity to PSGL-1, a sialomucin-like glycoprotein on myeloid cells. Binding of PSGL-1 to P-selectin may be essential for leukocytes to roll on P-selectin-expressing cells under shear forces.

The 85-kDa cytosolic PLA2 (cPLA2) is present in most cells and tissues and its structural and functional properties have been described. Different agonists, growth factors and cytokines activate cPLA2 to hydrolyze cellular phospholipids thereby providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor (PAF), the well-known mediators of inflammatory and allergic reactions. Recent studies discussed here suggest that cPLA2 is a receptor-regulated enzyme involved in the inflammatory response. Therefore, inhibitors of cPLA2 may be useful as therapeutic agents in the treatment of inflammatory diseases.

The recruitment of leukocyte populations to an area of inflammation is one of the most fundamental processes of immune reactivity, yet a number of the mechanisms which are important to this process are not clearly understood. Investigations directed at understanding the mechanisms of leukocyte elicitation have centered around classical chemotactic factors such as C5a and fMLP, however, these known agents have demonstrated little specificity for recruiting particular leukocyte populations. Recent advances in this field have been made with the discovery of a novel supergene family of chemotactic cytokines or chemokines. These cytokines are important as they possess a high degree of specificity for the recruitment of specific subpopulations of leukocytes.

The effects of PGE1 or 13,14-dihydro PGE1 (PGE0) on the expression of COX-2 protein and COX activity elicited by LPS (1 microgram/ml for 24 h) in bovine aortic endothelial cells (BAEC) and J774.2 macrophages were investigated. PGE1 or PGE0 (0.001 to 10 micrograms/ml) caused a dose-dependent decrease of COX activity elicited by LPS in both cell types. Western blot analysis showed that PGE1 or PGE0 (1 microgram/ml) inhibited the expression of COX-2 protein in LPS-activated BAEC and J774.2 macrophages. Thus, PGE1 or (its metabolite) PGE0 decrease the formation of COX metabolites by inhibiting the induction of COX-2 protein by LPS.

Sub-micromolar levels of the lipoxygenase products of n-3 fatty acids specifically antagonize both the contractile effects of thromboxane (U46619) and its platelet aggregating effect. In addition, OH-22:6n3 inhibits thromboxane-induced decreases in cerebral blood flow of the rat. Analysis of binding parameters indicates these derivatives induce a marked decrease in the affinity of the TXA2/PGH2 receptor for thromboxane with a mild change in the number of receptor sites. The 22-carbon n-3 hydroxy fatty acids are the most potent biological antagonists of thromboxane in comparison to the n-6 hydroxy fatty acids and their parent fatty acids. Dietary permutations modify the hydroxy fatty acid profile and correlate with changes in thromboxane-mediated responses.

A new method is introduced admitting of direct quantification of collagen-induced platelet trapping in the rat lung. The synthetic PG1(2)-mimetics, Iloprost and Cicaprost, are capable of inhibiting the trapping of platelets induced by collagen. The described method has proved to be suited for performing both pharmacodynamic and effectkinetic investigations with inhibitors of collagen-induced platelet trapping.